In this study, the expression patterns of zif268 and activity-regulated cytoskeleton-associated gene (
arc) were investigated in the basolateral amygdala (BLA) and dorsal hippocampal (
dHPC) subregions during context-induced
drug-seeking following 22 h or 15 d abstinence from
cocaine self-administration.
Arc and zif/268
mRNA in BLA and
dHPC increased after re-exposure to the
cocaine-paired chamber at both timepoints; however, only the BLA increases (with one exception-see below) were differentially affected by the presence or absence of the
cocaine-paired lever in the chamber. Following 22 h of abstinence,
arc mRNA was significantly increased in the BLA of
cocaine-treated rats re-exposed to the chamber only with levers extended, whereas following 15 d of abstinence,
arc mRNA in the BLA was increased in
cocaine-treated rats returned to the chamber with or without levers extended. In contrast, zif268
mRNA in the BLA was greater in
cocaine-treated rats returned to the chamber with levers extended vs. levers retracted only after 15 d of abstinence. In the dentate gyrus (DG) following 22 h of abstinence, zif268
mRNA was greater in rats returned to the chamber where levers were absent regardless of
drug treatment whereas
arc mRNA was increased in CA1 (cell bodies and dendrites) and CA3 only in
cocaine-treated groups. Following 15 d of abstinence,
arc mRNA was significantly greater in CA1 and CA3 of both
cocaine-treated groups returned to the chamber than in those placed into a familiar, non-salient alternate environment; however, only in CA1 cell bodies the
cocaine context-induced increases significantly greater than in yoked-saline controls. In contrast, zif/268
mRNA in all
dHPC regions was significantly greater in both
cocaine-treated groups returned to the
cocaine context than in the
cocaine-treated group returned to an alternative environment or saline-treated groups. These data suggest that the temporal dynamics of
arc and zif268 gene expression in the BLA and
dHPC encode different key elements of
drug context-induced
cocaine-seeking.